Notes

Full-Endoscopic Lumbar Discectomy regarding Frequent Lumbar Disk Herniation: A Retrospective Review together with Patient-Reported Outcome Measures.
higher insulin sensitivity and catabolic function. Such effects may be involved in bromocriptine therapeutic effects, given the impaired expression of dopamine receptors in the visceral adipose tissue of IR patients, as well as the correlation of D1R expression with InsR and metabolic mediators.
Bromocriptine treatment remodels adipose tissue and the liver dopaminergic system, with increased D1R and TH levels, resulting in higher insulin sensitivity and catabolic function. Such effects may be involved in bromocriptine therapeutic effects, given the impaired expression of dopamine receptors in the visceral adipose tissue of IR patients, as well as the correlation of D1R expression with InsR and metabolic mediators.
NRF2, a transcription factor that regulates cellular redox and metabolic homeostasis, plays a dual role in human disease. While it is well known that canonical intermittent NRF2 activation protects against diabetes-induced tissue damage, little is known regarding the effects of prolonged non-canonical NRF2 activation in diabetes. The goal of this study was to determine the role and mechanisms of prolonged NRF2 activation in arsenic diabetogenicity.

To test this, we utilized an integrated transcriptomic and metabolomic approach to assess diabetogenic changes in the livers of wild type, Nrf2
, p62
, or Nrf2
; p62
mice exposed to arsenic in the drinking water for 20 weeks.

In contrast to canonical oxidative/electrophilic activation, prolonged non-canonical NRF2 activation via p62-mediated sequestration of KEAP1 increases carbohydrate flux through the polyol pathway, resulting in a pro-diabetic shift in glucose homeostasis. This p62- and NRF2-dependent increase in liver fructose metabolism and gluconeogenesis occurs through the upregulation of four novel NRF2 target genes, ketohexokinase (Khk), sorbitol dehydrogenase (Sord), triokinase/FMN cyclase (Tkfc), and hepatocyte nuclear factor 4 (Hnf4A).

We demonstrate that NRF2 and p62 are essential for arsenic-mediated insulin resistance and glucose intolerance, revealing a pro-diabetic role for prolonged NRF2 activation in arsenic diabetogenesis.
We demonstrate that NRF2 and p62 are essential for arsenic-mediated insulin resistance and glucose intolerance, revealing a pro-diabetic role for prolonged NRF2 activation in arsenic diabetogenesis.
Glucagon-like peptide-1 and glucagon receptor (GLP-1R/GCGR) co-agonism can maximise weight loss and improve glycaemic control in type 2 diabetes and obesity. In this study, we investigated the cellular and metabolic effects of modulating the balance between G protein and β-arrestin-2 recruitment at GLP-1R and GCGR using oxyntomodulin (OXM)-derived co-agonists. This strategy has been previously shown to improve the duration of action of GLP-1R mono-agonists by reducing target desensitisation and downregulation.

Dipeptidyl dipeptidase-4 (DPP-4)-resistant OXM analogues were generated and assessed for a variety of cellular readouts. Molecular dynamic simulations were used to gain insights into the molecular interactions involved. Invivo studies were performed in mice to identify the effects on glucose homeostasis and weight loss.

Ligand-specific reductions in β-arrestin-2 recruitment were associated with slower GLP-1R internalisation and prolonged glucose-lowering action invivo. The putative benefits of GCGR agonism were retained, with equivalent weight loss compared to the GLP-1R mono-agonist liraglutide despite a lesser degree of food intake suppression. The compounds tested showed only a minor degree of biased agonism between G protein and β-arrestin-2 recruitment at both receptors and were best classified as partial agonists for the two pathways measured.

Diminishing β-arrestin-2 recruitment may be an effective way to increase the therapeutic efficacy of GLP-1R/GCGR co-agonists. These benefits can be achieved by partial rather than biased agonism.
Diminishing β-arrestin-2 recruitment may be an effective way to increase the therapeutic efficacy of GLP-1R/GCGR co-agonists. These benefits can be achieved by partial rather than biased agonism.
Previous studies of radiofrequency catheter ablation (RFA) of ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), relying on limited numbers of procedures, have not reported VT-free survival in parallel for single and multiple procedures (ie, after the last procedure). Data regarding the impact of RFA on VT burden are scarce.

The purpose of this study was to provide new insights on clinical outcomes based on a large series of VT ablation procedures from the current era in ARVC patients.

We evaluated consecutive patients with definite ARVC who underwent RFA procedures between 2009 and 2019 at our center. We assessed VT-free survival, for single and multiple procedures, and changes in VT burden and antiarrhythmic drugs (AADs) after RFA.

Among 116 patients, there were 166 RFA procedures, 106 (63.9%) of which involved epicardial ablation. Cumulative freedom from VT after a single procedure was 68.6% and 49.8% at 1 and 5 years, respectively. Cumulative VT-free survival after multiple procedures was 81.8% and 69.6% at 1 and 5 years, respectively. AGK2 VT burden per RFA was reduced after vs before ablation (mean 0.7 vs 10.0 events/year; P <.001). Furthermore, VT burden per patient was reduced after last ablation vs before first ablation (mean 0.5 vs 10.9 events/year; P <.001). Use of AADs decreased after ablation (22.2% vs 51.9%; P <.001).

In ARVC patients, RFA provided good VT-free survival after a single procedure, with multiple procedures required for more sustained freedom from VT recurrence. Marked reduction in VT burden permitted discontinuation of AADs.
In ARVC patients, RFA provided good VT-free survival after a single procedure, with multiple procedures required for more sustained freedom from VT recurrence. Marked reduction in VT burden permitted discontinuation of AADs.
Communication breakdown is one of the main causes of adverse events in clinical routine. The main objective of this study was to assess whether a short training course on medical communication based on the situation-background-assessment-recommendation (SBAR) tool improved the quality of communication in clinical practice.

Interventional study, conducted at the Jeanne de Flandre maternity unit (Lille University Hospital, France) between January 2017 and December 2019. The training sessions lasted 1 hour and consisted of a theoretical part, based on the SBAR tool, and of a practical part (video-stimulated recall and role-play case scenarios). The main outcome measure was the evaluation of the quality of the telephone calls made by a caregiver to the on-call doctor, using a questionnaire completed before (Q1) and remotely from training (Q2).

One hundred and twenty health professionals were trained (n=120). Following the trainings, there was an improvement in communication in the short term, whether in terms of relevance (64.
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